NF-κB activation is a turn on for vaccinia virus phosphoprotein A49 to turn off NF-κB activation

Proceedings of the National Academy of Sciences of the United States of America
Sarah NeidelGeoffrey L Smith

Abstract

Vaccinia virus protein A49 inhibits NF-κB activation by molecular mimicry and has a motif near the N terminus that is conserved in IκBα, β-catenin, HIV Vpu, and some other proteins. This motif contains two serines, and for IκBα and β-catenin, phosphorylation of these serines enables recognition by the E3 ubiquitin ligase β-TrCP. Binding of IκBα and β-catenin by β-TrCP causes their ubiquitylation and thereafter proteasome-mediated degradation. In contrast, HIV Vpu and VACV A49 are not degraded. This paper shows that A49 is phosphorylated at serine 7 but not serine 12 and that this is necessary and sufficient for binding β-TrCP and antagonism of NF-κB. Phosphorylation of A49 S7 occurs when NF-κB signaling is activated by addition of IL-1β or overexpression of TRAF6 or IKKβ, the kinase needed for IκBα phosphorylation. Thus, A49 shows beautiful biological regulation, for it becomes an NF-κB antagonist upon activation of NF-κB signaling. The virulence of viruses expressing mutant A49 proteins or lacking A49 (vΔA49) was tested. vΔA49 was attenuated compared with WT, but viruses expressing A49 that cannot bind β-TrCP or bind β-TrCP constitutively had intermediate virulence. So A49 promotes virulence by inhibiting NF-κB activation and ...Continue Reading

References

Jun 1, 1990·Journal of Virology·F G Falkner, B Moss
Nov 1, 1990·Virology·S J GoebelE Paoletti
Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·A BowieL A O'Neill
Dec 17, 2002·Molecular and Cellular Biology·Valerie LangSteven C Ley
Feb 5, 2003·The Journal of Experimental Medicine·Mary T HarteLuke A J O'Neill
Jan 14, 2004·The Journal of General Virology·Caroline GubserGeoffrey L Smith
Mar 16, 2005·The Journal of Experimental Medicine·Julianne StackAndrew G Bowie
Apr 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yoshinori KanemoriNoriyuki Sagata
Dec 13, 2005·Molecular & Cellular Proteomics : MCP·Eiji KinoshitaTohru Koike
Nov 25, 2006·Protein Science : a Publication of the Protein Society·Mika AoyagiRobert C Liddington
Feb 13, 2008·PLoS Pathogens·Ron A-J ChenGeoffrey L Smith
Mar 23, 2012·Immunological Reviews·Naama Kanarek, Yinon Ben-Neriah
Sep 4, 2013·The Journal of General Virology·Geoffrey L SmithRebecca P Sumner
Dec 21, 2013·The Journal of Biological Chemistry·Sofiya FedosyukTim Skern
Dec 29, 2013·Journal of Virology·Rebecca P SumnerGeoffrey L Smith
Jan 22, 2015·The Journal of Biological Chemistry·Sarah NeidelStephen C Graham
Oct 24, 2017·The Journal of General Virology·Carlos Maluquer de Motes, Geoffrey L Smith

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Citations

Feb 27, 2020·The Journal of General Virology·Sarah NeidelGeoffrey L Smith
Oct 7, 2020·The FEBS Journal·Yanli BiYongchao Zhao
Oct 30, 2020·Frontiers in Immunology·Misbah El-JesrCarlos Maluquer de Motes
Dec 31, 2020·Pathogens·Chathura D SuraweeraMarc Kvansakul
Aug 29, 2021·Pathogens·Sian Lant, Carlos Maluquer de Motes

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Methods Mentioned

BETA
electrophoresis
immunoprecipitation

Software Mentioned

GraphPad Prism
GraphPad

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